VPA axial malformations are related to embryonic somitic histone hyperacetylation. In cancer, histone hyperacetylation activates apoptosis. To verify if apoptosis is involved in somitic abnormalities, VPA-exposed embryos were evaluated for DNA fragmentation and for pro- (p53, acetylated p53, caspase 3) and anti-apoptotic (Sirt 1) protein expression. Pregnant mice were i.p. dosed on day 8 with VPA 400 mg/kg or TSA (16 mg/kg). Embryos, collected 3, 5, 9 or 24 h after treatment, were examined and processed for apoptosis or protein analysis. An event cascade has been observed at the level of somites and proposed as related to VPA-induced axial skeletal defects: increased p53 (3 h), DNA fragmentation (9 h), abnormalities (24 h). TSA, used as alternative HDAC inhibitor, induced apoptosis and somitic abnormalities, strengthening our hypothesized link between HDAC inhibition and axial defects.
VPA-related axial skeletal defects and apoptosis: a proposed event cascade / F. Di Renzo, M.L. Broccia, E. Giavini, E. Menegola. - In: REPRODUCTIVE TOXICOLOGY. - ISSN 0890-6238. - 29:1(2010), pp. 106-112.
|Titolo:||VPA-related axial skeletal defects and apoptosis: a proposed event cascade|
DI RENZO, FRANCESCA (Primo)
BROCCIA, MARIALUISA (Secondo)
GIAVINI, ERMINIO (Penultimo)
MENEGOLA, ELENA (Ultimo)
|Parole Chiave:||Embryo; Mechanisms; Mouse; p53; Skeletal malformations; Somites; Valproic acid|
|Settore Scientifico Disciplinare:||Settore BIO/06 - Anatomia Comparata e Citologia|
|Data di pubblicazione:||2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.reprotox.2009.10.004|
|Appare nelle tipologie:||01 - Articolo su periodico|